Peripheral blood leukocytes (PBL) from AIDS patients but not from asymptomatic HIV-infected (HIV+) individuals exhibit two distinct types of antigen presenting cell (APC) defects. PBL from children infected with HIV exhibit the same complex spectrum of T helper cell (Th) defects that we reported in adult patients. PBL from healthy HIV- children do not generate Th responses to recall until 2 years of age, although T cell responses to HLA alloantigens (ALLO) and phytohemagglutinin (PHA) are strong at birth. The early defect in Th responses to recall antigens seen in HIV+ adults and children is associated with a non-HIV inhibitory factor that is produced by CD8+ cells and is selective in its action in that it only suppresses HLA self-restricted Th responses. PBL from volunteers immunized with a candidate AIDS vaccine generate potent HIV-specific T helper and effector responses, even one year after immunization. Using our in vitro Th tests, we can detect long-term improvement in Th function in more than 50% of patients on AZT, ddI, or soluble CD4-IgG therapy. We can detect evidence of HIV exposure by sensitive HIV-specific T cell tests, using PBL from high risk HIV seronegative cohorts who are also HIV- by the polymerase chain reaction. Studies of patients with primary immune deficiencies exhibit defects in Th and APC function. Patients with Wiskott-Aldrich Syndrome exhibit a defect that involves an unstable immunogenic complex that is formed by self HLA class I, beta2-microglobulin and antigenic peptide.